3,5-Di-t-butyl-4-hydroxyanisole (DTBHA) increased in a concentration-dependent manner (calculated pEC(50) = 4.55 +/- 0.18 M) the oxalate-stimulated Ca(2+)-pumping rate of rat skeletal muscle sarcoplasmic reticulum (SR) vesicles. Kinetic analysis of this effect suggested that the activation of SR Ca(2+)-ATPase operated by (DTBHA) was of both mixed and non-competitive type with respect to ATP in the range of concentrations 0.1-0.5 mM and above 1 mM, respectively; furthermore, it was independent of the free Ca(2+) concentrations. This indicated that the enzyme activation took place through the acceleration of the enzyme-substrate complex breakdown. Moreover, it appeared that its target site was cyclopiazonic acid sensitive. The uncommon ability of (DTBHA) to upregulate SR Ca(2+) uptake is of interest in view of its possible use for treating pathological conditions characterised by cell Ca(2+) overload as well as genetic disorders where SR Ca(2+) homeostasis is altered.

Fusi, F., Tzankova, V., Valoti, M., Pessina, F., Sgaragli, G.P. (2001). 3,5-Di-t-butyl-4-hydroxyanisole (DTBHA) activation of rat skeletal muscle sarcoplasmic reticulum Ca2+-ATPase. BIOCHEMICAL PHARMACOLOGY, 62(12), 1613-1619.

3,5-Di-t-butyl-4-hydroxyanisole (DTBHA) activation of rat skeletal muscle sarcoplasmic reticulum Ca2+-ATPase.

FUSI, FABIO;VALOTI, MASSIMO;PESSINA, FEDERICA;SGARAGLI, GIAN PIETRO
2001-01-01

Abstract

3,5-Di-t-butyl-4-hydroxyanisole (DTBHA) increased in a concentration-dependent manner (calculated pEC(50) = 4.55 +/- 0.18 M) the oxalate-stimulated Ca(2+)-pumping rate of rat skeletal muscle sarcoplasmic reticulum (SR) vesicles. Kinetic analysis of this effect suggested that the activation of SR Ca(2+)-ATPase operated by (DTBHA) was of both mixed and non-competitive type with respect to ATP in the range of concentrations 0.1-0.5 mM and above 1 mM, respectively; furthermore, it was independent of the free Ca(2+) concentrations. This indicated that the enzyme activation took place through the acceleration of the enzyme-substrate complex breakdown. Moreover, it appeared that its target site was cyclopiazonic acid sensitive. The uncommon ability of (DTBHA) to upregulate SR Ca(2+) uptake is of interest in view of its possible use for treating pathological conditions characterised by cell Ca(2+) overload as well as genetic disorders where SR Ca(2+) homeostasis is altered.
Fusi, F., Tzankova, V., Valoti, M., Pessina, F., Sgaragli, G.P. (2001). 3,5-Di-t-butyl-4-hydroxyanisole (DTBHA) activation of rat skeletal muscle sarcoplasmic reticulum Ca2+-ATPase. BIOCHEMICAL PHARMACOLOGY, 62(12), 1613-1619.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11365/43742
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